This proposal is to study diabetic pregnancies and the developmental changes which occur in infants of insulin dependent and gestatonally diabetic mothers. The minor glycosylated hemoglobin AIc (Hb AIc) will be followed through such pregnancies in order to determine possible implications to oxygen transport, its value in prognosticating changes in the infant when maternal glucose intolerance exists, its use as an indication for treating maternal glucose intolerance in the third trimester, and for diagnostic value in large neonates where post-partum maternal glucose tolerance has reverted to normal. We have studied Hb AIc in pregnant diabetics and found it to be elevated in both insulin dependent and gestationally diabetic pregnant women. The levels in the pregnant diabetics were elevated compared to pregnant normals, but lower than in the non-pregnant insulin dependent diabetics. Since Hb AIc has an increased affinity for oxygen, it may be disadvantageous to the fetus. The lower levels of Hb AIc in pregnant diabetics may reflect either a better state of diabetic control and/or a compensatory mechanism to protect the fetus. In preliminary studies, we have shown a correlation between third trimester Hb AIc and macrosomia in infants of diabetic mothers. In the present study we are interested in characterizing the sequential changes in hemoglobin AIc, correlating those changes with infant macrosomia and evaluating the physiological significance of hemoglobin AIc during human pregnancy by studying hemoglobin oxygen affinity (e.g., oxygen dissociation curves and P50) and factors which modify it (e.g., 2,3-DPG, plasma and intracellular inorganic phosphate, pH of whole blood and intracellular pH). Similar studies will be pursued in pregnant primates with streptozotocin induced diabetes.